Needle assembly for mixing of substances

ABSTRACT

In one aspect of the invention, a needle assembly is provided, including: a body having a proximal end, a distal end, and a channel located therebetween, the body being configured to be mounted to an injector; a needle fixed to the body, the needle having proximal and distal ends, the distal end extending distally from the distal end of the body and being formed for insertion into a patient, the proximal end of the needle being in communication with the channel; and, a filter disposed in the channel proximally of the proximal end of the needle. Advantageously, a needle assembly is provided which permits mixing of at least two substances in preparation for injection, without modification to the associated injector.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation of U.S. patent application Ser. No.13/810,675, filed Jan. 17, 2013, which is the U.S. national stage ofinternational patent application number PCT/US10/42876, filed Jul. 22,2010. Each of the disclosures of these applications is herebyincorporated herein by reference in its entirety

FIELD OF THE INVENTION

This invention relates to needle assemblies for mixing of at least twosubstances in preparation for medical injection.

BACKGROUND OF THE INVENTION

Certain drugs or medicaments (those terms being used interchangeablyherein) are preferably provided in powder or dry form (such as alyophilized form), and require reconstitution prior to administration.Lyophilized drugs, for example, typically are supplied in a freeze-driedform that needs to be mixed with a diluent to reconstitute the substanceinto a form that is suitable for injection. Medicaments may also beprovided in other dry or powder form that require reconstitution.

In addition, drugs may be provided as multipart systems which requiremixing prior to administration. For example, one or more liquid (e.g.,flowable (slurry or liquid)) components, and/or dry (e.g., powdered orgranular) components may be provided in a drug container or deliverydevice which require mixing prior to administration. The components canbe mixed and used to form various administratable drugs, such asinsulin.

Prior art devices have been developed that provide a wet component(e.g., liquid) and a dry component (e.g., powder) in separate chambersof a common container with the container being configured to permit theflow of the wet component to the dry component to cause mixing thereofin preparing an administratable solution for injection. U.S. Pat. No.4,874,381 to Vetter is directed to an injector having a barrelconfigured for mixing, while U.S. Pat. No. 4,968,299 to Ahlstrand et al.is directed to a drug cartridge having a barrel configured for mixing.Both Vetter et al. and Ahlstrand et al. disclose typical configurationsfor mixing where a bypass channel is formed in the barrel of the device.As such, the device must be specifically configured for mixing.

SUMMARY OF EMBODIMENTS OF THE INVENTION

In one aspect of the invention, a needle assembly is provided,including: a body having a proximal end, a distal end, and a channellocated therebetween, the body being configured to be mounted to aninjector; a needle fixed to the body, the needle having proximal anddistal ends, the distal end extending distally from the distal end ofthe body and being formed for insertion into a patient, the proximal endof the needle being in communication with the channel; and, a filterdisposed in the channel proximally of the proximal end of the needle.Advantageously, a needle assembly is provided which permits mixing of atleast two substances in preparation for injection, without modificationto the associated injector.

Another aspect of the invention provides a needle assembly, including: abody having a proximal end, a distal end, and a channel locatedtherebetween, the body being configured to be mounted to an injector; aneedle fixed to the body, the needle having proximal and distal ends,the distal end extending distally from the distal end of the body andbeing formed for insertion into a patient, the proximal end of theneedle being in communication with the channel; and a rupturablemembrane disposed in the channel proximally of the proximal end of theneedle.

As used herein, the term “distal”, and derivatives thereof, shall referto a direction towards a patient during use, and the term “proximal”,and derivatives thereof, shall refer to a direction away from a patientduring use.

These and other features of the invention will be better understoodthrough a study of the following detailed description and accompanyingdrawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of a needle assembly formed in accordancewith the subject invention mounted onto an injector;

FIG. 2 is a cross-section of an embodiment of a needle assembly formedin accordance with the subject invention;

FIG. 3 is a cross-section of a second embodiment of a needle assemblyformed in accordance with the subject invention;

FIG. 4 is a schematic showing mixing of two substances in a needleassembly formed in accordance with the subject invention; and,

FIG. 5 shows alternative configurations for a needle assembly formed inaccordance with the subject invention.

DETAILED DESCRIPTION OF EMBODIMENTS OF THE PRESENT INVENTION

With reference to the figures, a needle assembly 10 is provided hereinformed to permit mixing of at least two substances in preparation forinjection. The needle assembly 10 is formed as a stand-alone componentwhich is mountable to a standard, un-modified medical injector, such asa syringe or pen injector. With reference to FIGS. 1 and 2, the needleassembly 10 is shown in connection with a medical injector I in the formof a syringe. In FIG. 3, the needle assembly 10 is shown in connectionwith the medical injector I being in the form of a pen injector. As willbe appreciated by those skilled in the art, the medical injector I canbe in the form of any known injector.

With reference to the figures, the needle assembly 10 generally includesa body 12, a needle 14, and at least one filter 16.

The body 12 includes a proximal end 18, a distal end 20 and a channel 22located therebetween. The channel 22 may be located at any mid-pointlength of the body 12, and preferably extends through the proximal end18 of the body 12 and distally therefrom. The body 12 may be formed ofvarious materials, but is preferably formed of a material compatiblewith the substance to be contained therein, as described below. The body12 may be formed of glass, thermoplastic, ceramic, metal andcombinations thereof.

Preferably, the needle assembly 10 is removably mountable to the medicalinjector I. In this manner, the needle assembly 10 may be disposed ofafter use, particularly with the needle 14 being consideredbiohazardous. As being removably mountable, the medical injector I maybe re-used with a subsequent needle assembly 10 or with a differentneedle assembly. This may be particularly desirable where the medicalinjector I is in the form of a pen injector. To permit removablemounting, one or more mounting features 24 may be formed on the body 12,particularly in proximity to the proximal end 18 thereof. As known inthe art, the mounting features 24 may be in the form of a luerarrangement (FIG. 2) and/or a thread arrangement (FIG. 3). Cooperatingfeatures 26 may be formed on the medical injector I configured to coactwith the mounting features 24 in having the needle assembly 10 beremovably mounted onto the medical injector 10. The cooperating features26 may be a luer and/or thread arrangement formed to cooperate with themounting features 24. Other cooperating mounting arrangements permittingremoval mounting known in the art may likewise be utilized.Alternatively, the body 12 may be rigidly fixed to the medical injectorI, such as by fusion, adhesion, and/or mechanical connection. With fixedmounting, the needle assembly 10 will be disposed of with the medicalinjector I as a single-use device.

The needle 14 may be of any standard type and includes a proximal end 28and a distal end 30, formed for insertion into a patient. The needle 14is fixed to the body 12 with the distal end 30 extending distally fromthe distal end 20 of the body 12. The proximal end 28 is formed to be incommunication with the channel 22.

The channel 22 is formed to accommodate at least one substance 32intended for mixing with at least one other secondary substance. Thesubstance 32 may be in dry form (powdered or granular) or in wet form(liquid or slurry) and may include one or more pharmaceutically-activeagents. The substance 32 is intended for mixing with one or moresecondary substances 34 accommodated in the medical injector I. Withactuation of the medical injector I, the one or more secondarysubstances 34 are urged therefrom and into the needle assembly 10,particularly into the channel 22. Interaction of the substances 32, 34results in mixing thereof as described below.

The filter 16 is porous and may be formed of any material compatiblewith the substance 32. The filter 16 is preferably located between theproximal end 18 of the needle 14 and the substance 32. With thisarrangement, the filter 16 provides a barrier for the substance 32 andavoids compaction of the needle 14 into the substance 32. In addition,it is preferred that the filter 16 be configured so as to provide abarrier in maintaining the substance 32 within the channel 22. Thus, theoverall porosity of the filter 16 should be configured to not permitpassage therethrough of the substance 32. The porosity of the filter 16may be configured based on various variables including pore size, lengthof the filter, extent of open/closed network of the pores and so forth.

Depending on how the needle assembly 10 is packaged, a porous secondfilter 36 may be provided in the channel 22 located proximally of thesubstance 32. The second filter 36 may be configured with the sameconsiderations as noted above with respect to the filter 16.Alternatively, as discussed below, a film or other barrier may beapplied across the channel 22 to provide a proximal barrier for thesubstance 32.

The filter 16 and the second filter 36 may be formed of variousmaterials which are compatible with the substance 32. The needleassembly 10 may act as a storage container, where the substance 32 ismaintained in the channel 22 for an extended period of time prior touse. With this arrangement, it is desired to have minimal, ideally no,chemical interactions between the filter 16/second filter 36 and thesubstance 32. The filter 16/second filter 36 may be formed of variousmaterials, including, but not limited to thermoplastic, glass, ceramic,metal and combinations thereof. By way of non-limiting example, thefilter 16 and the second filter 36 may be formed from a porous plasticfilter, such as Porex porous filter (e.g., Catalogue No. X-5923, 18 to40 micron std. pipette filter PE).

As indicated above, the substance 32 is maintained in the needleassembly 10 ready for mixing with the one or more secondary substances34 located in the medical injector I. The one or more secondarysubstances 34 will be in a wet form (e.g., liquid or slurry) andselected to act as a diluent for, and/or as a compatible component aspart of a multipart system with, the substance 32. With the needleassembly 10 being mounted to the medical injector I, the one or moresecondary substances 34 may be urged from the medical injector I intothe channel 22. With reference to FIG. 2, with the medical injector Ibeing of a syringe type, the one or more secondary substances 34 may beurged directly from syringe tip 38 into the channel 22. Preferably, thesecond filter 36 is located between the substance 32 and the syringe tip38.

The one or more secondary substances 34 are forced into the channel 22under pressure generated by the medical injector I. The medical injectorI generates pressure in administering the one or more secondarysubstances 34 as is well known in the art. The pressure generated by themedical injector I will urge the one or more secondary substances 34towards the proximal end 28 of the needle 14. It is preferred that thefilter 16, the channel 22, and the second filter 36 be configured toprovide sufficient dwell time of the one or more secondary substances34, with exposure to the substance 32, to ensure sufficient mixing priorto administration. If insufficient dwell time is provided, aninsufficiently mixed solution may be administered.

In the preferred arrangement, it is preferred that the porosity of thesecond filter 36 be greater than the porosity of the filter 16. Withreference to FIG. 4, with the second filter 36 be greater in porositythan the filter 16, the one or more secondary substances 34 may be urgedthrough the second filter 36 more readily than through the filter 16.This will result in more restriction at the filter 16 than at the secondfilter 36. The level of restriction may be used to set the dwell time ofthe one or more secondary substances 34 in the channel 22. Accordingly,as represented by the arrows, the one or more secondary substances 34will experience some turbulence in being exposed to the substance 32.The turbulence causes mixing of the substances 32, 34. With furtherpressure from the medical injector I during actuation, a mixed solution40 will be caused to pass through the filter 16 with further passagethrough the needle 14 for administration. Mix characteristics of thesubstances 32, 34 (solubility, viscosity, etc.), as well as the physicaldimensioning and configuration of the channel 22 and the filters 16, 36,must be considered in ensuring that sufficient mixing may be achieved inpreparing the mixed solution 40 for administration.

Dwell time may be varied with variation in restriction to flow betweenthe filter 16 and the second filter 36 as described above. Mixing may beconducted in-flow through the channel 22 as described above. Inaddition, or alternatively, a portion of the one or more secondarysubstances 34 may be urged into the channel 22 from the medical injectorI without fully pressurizing the channel 22. In this manner, an amountof the one or more secondary substances 34 may be disposed into thechannel 22 without any flow urged through the filter 16. The needleassembly 10 may be then agitated, e.g., by shaking or rolling, to causemixing of the substances 32, 34. The medical injector I may then becaused to further urge the one or more secondary substances 34 therefromin pressurizing the channel 22 and causing flow through the filter 16.

The substances 32, 34 may be mixed in-flow where all of the one or moresecondary substances 34 are caused to be dispensed from the medicalinjector I in a continuous flow. The substances 32, 34 mix inside thechannel 22 and the mixed solution 40 is administered. With in-flowmixing, it is preferred that the mixing be conducted with the needle 14inserted into a patient for injection. Thus, for use, the needleassembly 10 is mounted on the medical injector I. The needle 14 isinserted into a patient, and the medical injector I is caused to beactuated. The medical injector I is configured such that, with anactuation of the medical injector I, a sufficient quantity of the one ormore secondary substances 34 is urged from the medical injector I undersufficient pressure to cause sufficient mixing and administration of themixed solution 40. Advantageously, the needle assembly 10 may be usedwith the medical injector I being in a standard, un-modified form toachieve mixing, including possible reconstitution.

Alternatively, the mixed solution 40 may be at least partially preparedprior to injection with the needle assembly 10 being mounted on themedical injector I. Here, sufficient quantity of the one or moresecondary substances 34 may be urged from the medical injector I andinto the channel 22. With agitation of the needle assembly 10 maintainedon the medical injector I, sufficient mixing of the mixed solution 40may be achieved prior to injection. Thereafter, the needle 14 may beinserted into a patient and injection administered.

Concerns may exist over gases trapped in the channel 22, particularlyresulting from mixing. Vents may be provided on the in-flow mixingarrangement to allow release of any trapped gases from the channel 22during injection. With the prior mixing arrangement, the medicalinjector I may be held in an upright position and partially activated topermit venting and achieve priming of the needle 14 prior to injection.Once primed, injection may be administered.

In-flow mixing or prior mixing may be selected based on the mixcharacteristics of the substances 32, 34. With the substance 32 beinghighly soluble (e.g., ALP powders), in-flow mixing may be utilized,whereas, with the substance 32 being less soluble, prior mixing may beutilized. ALP powders are ultra-light powders which may be formed by theprocess described in U.S. Published Appl. No. 2008/0226729 A1, theentire contents of which are incorporated by reference herein. Otherpowders, such as lyophilized powders, may be used with the subjectinvention.

With the medical injector I being of a syringe type, the second filter36 need not be utilized. A removal barrier 41 (shown in dashed lines inFIG. 2), which may be in the form of a removable film, foil or plug, maybe utilized to seal the proximal end of the channel 22 prior to use. Inpreparation for use, the removal barrier 41 is removed. The filter 16provides restriction against flow, thus, permitting turbulence inmixing, as described above.

With reference to FIG. 3, the needle assembly 10 may be configured to beused with the medical injector I in the form of a pen injector. Here, asecond needle 42 is provided having a proximal end 44 and a distal end46. The second needle 42 is fixed to the body 12 with the distal end 46being in communication with the channel 22. It is preferred that thesecond filter 36 be utilized with a pen injector configuration of theneedle assembly 10 and that the second filter 36 be located between thesubstance 32 and the distal end 46 of the second needle 42. In thismanner, compaction of the second needle 42 into the substance 32 may beavoided. Also, the second filter 36 acts as a proximal barrier forretaining the substance 32 within the channel 22.

The second needle 42 is configured so that the proximal end 44 hassufficient length to fully penetrate any septum 48 closing off the oneor more secondary substances 34 in the medical injector I, with theneedle assembly 10 being mounted to the medical injector I.

With the medical injector I in use as a pen injector, the one or moresecondary substances 34 are urged through the second needle 42 and intothe channel 22 during use. The substances 32, 34 mix in the same fashionas described above. The medical injector I may be of any standard,un-modified type and still be workable with the needle assembly 10.

To facilitate preparation of the needle assembly 10, it is preferredthat the body 12 be modularly formed of at least two body components12A, 12B. Preferably, the body components 12A, 12B are joined at a joint50 located in the proximal back-half section of the channel 22. In thismanner the fore body component 12A, which houses the distal section ofthe channel 22, may be prepared with the filter 16 and the substance 32.Thereafter, the second filter 36, if being used, may be disposed intothe channel 22 in the fore body component 12A or into the channel 22 inthe aft body component 12B. The fore and aft body components 12A, 12Bare joined at the joint 50 using any known technique, such as by fusion,adhesion and/or mechanical connection. It is preferred that the joint 50be at least liquid tight. The needle 14 and the second needle 42 may befixed to the body components 12A, 12B in any sequence and with any knowntechnique. Alternatively, the substance 32 may be disposed into thechannel 22 in the aft body component 12B with the fore body component12A being mounted thereto. It is further noted that the body 12 may bedivided into further body components, such as tertiary body component12C (FIG. 2), joined to the fore body component 12A at joint 50B. Thetertiary body component 12C may have the needle 14 fixed thereto. Assuch, the needle 14 may be prepared and assembled separately from thesubstance 32 in the fore and aft body components 12A, 12B.

With reference to FIG. 5, one or more rupturable membranes 52 may beutilized in the channel 22 in lieu of, or in addition to, the filter 16and the second filter 36. The rupturable membranes 52 may be utilizedwhere the substance 32 is in a wet form (liquid or slurry).

The rupturable membranes 52 may be configured to rupture under pressurefrom the flow of the one or more secondary substances 34. The membranes52 may be configured to readily rupture with turbulence being caused bythe filter 16, with or without the second filter 36, as described above.Alternatively, the membranes 52 may be used in place of the filter 16and/or the second filter 36 such that the rupture threshold of therespective membranes 52 is configured to provide equivalent resistanceto flow in the same manner as the filter 16 and the second filter 36.For example, a first membrane 52A may be utilized alone in the channel22, at the location of the filter 16, which is set to rupture upon apredetermined pressure build-up in the channel 22. This pressurebuild-up permits mixing of the substances 32, 34. With a second membrane52B, the second membrane 52B may be configured to more readily rupturethan the first membrane 52A; this provides an equivalent arrangement tothe second filter 36 being more porous than the filter 16. If themembranes 52 are used in conjunction with the filter 16, and optionallythe second filter 36, it is preferred that the membranes 52 provide theleast resistance against flow through the channel 22. With thisarrangement, the membranes 52 would readily rupture and permit the firstfilter 16 and the second filter 36, if used, to create turbulence inpermitting mixing of the substances.

The membranes 52 are liquid impervious and may be formed of variousrupturable materials, such as films and/or foils. The membranes 52 maybe utilized to contain the substance 32 within the needle assembly 10.This is particularly useful where the substance 32 is in wet form.

The needle assembly 10 may also include a needle shield 54 formed tocover the distal end 30 of the needle 14 when not in use. The needleshield 54 may cover the distal end 30 before and/or after use of theneedle 14. The needle shield 54 may be formed with any knownconfiguration and may have releasable mounting features for releasablyretaining onto the body 12 and/or the needle 14. For example, the needleshield 54 may include an elastomeric inner liner into which the needle14 is embedded with the needle shield 54 being mounted thereabout. Inaddition, or alternatively, the needle shield 54 may include mountingfeatures, such as detents or grooves, which permit snap mounting ontothe body 12.

What is claimed is:
 1. A needle assembly comprising: a body having aproximal end, a distal end, and a channel located therebetween, the bodybeing configured to be mounted to an injector; a needle fixed to thebody, the needle having proximal and distal ends, the distal endextending distally from the distal end of the body and being formed forinsertion into a patient, the proximal end of the needle being incommunication with the channel; and a filter disposed in the channelproximally of the proximal end of the needle; and a second filterdisposed proximally of the filter in the channel; wherein at least oneof the first and second filters is fixedly disposed within the channel.2. The needle assembly of claim 1, wherein the first and second filtersare fixedly disposed within the channel.
 3. The needle assembly of claim1, wherein the second filter is more porous than the filter.
 4. Theneedle assembly of claim 1, further comprising a shield to cover thedistal end of the needle.
 5. The needle assembly of claim 1, furthercomprising one or more mounting features to removably attach the body toan injector.
 6. The needle assembly of claim 5, wherein the mountingfeatures include one or more selected from the group consisting of: aluer arrangement; a threaded arrangement; and combinations thereof. 7.The needle assembly of claim 1, further comprising a second needle fixedto the body, the second needle having proximal and distal ends, thedistal end of the second needle being in communication with the channel.8. The needle assembly of claim 7, further comprising a second filterdisposed between the filter and the distal end of the second needle inthe channel.
 9. The needle assembly of claim 8, wherein the secondfilter is more porous than the filter.
 10. The needle assembly of claim1, wherein, said filter is porous and configured so that liquid locatedin the channel proximally of said filter may flow through said filter.